{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T18:43:28Z","timestamp":1773427408743,"version":"3.50.1"},"reference-count":28,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2011,6]]},"abstract":"<jats:p> Cell-cycle induction in hepatocytes protects from prolonged tissue damage after toxic liver injury. Early growth response ( Egr) -1<jats:sup>\u2212\/\u2212<\/jats:sup> mice exhibit increased liver injury after carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>) exposure and reduced TNF-\u03b1 production. Because TNF-\u03b1 is required for prompt cell-cycle induction after liver injury, here, we tested the hypothesis that Egr-1 is required for timely hepatocyte entry into the cell cycle after CCl<jats:sub>4<\/jats:sub>-induced liver injury. Acute liver injury was induced by a single injection of CCl<jats:sub>4<\/jats:sub>. Assays were employed to assess indices of the cell cycle in liver after CCl<jats:sub>4<\/jats:sub> exposure. Bromodeoxyuridine incorporation peaked in wild-type mice at 48 h after CCl<jats:sub>4<\/jats:sub> but was reduced by 80% in Egr-1<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Proliferating-cell nuclear-antigen immunohistochemistry revealed blocks in cell-cycle entry and progression to DNA synthesis in Egr-1-deficient mice 48 h after CCl<jats:sub>4<\/jats:sub>. Cyclin D, important for G0\/G1 progression, was reduced at baseline and 36 h after CCl<jats:sub>4<\/jats:sub>. Cyclin E1, required for G1\/S-phase transition, was reduced in Egr-1<jats:sup>\u2212\/\u2212<\/jats:sup> mice 24 and 48 h after CCl<jats:sub>4<\/jats:sub> exposure and was associated with reduced phosphorylation of the retinoblastoma protein. Proliferation in Egr-1<jats:sup>\u2212\/\u2212<\/jats:sup> mice was delayed, rather than blocked, because indices of cell-cycle progression were restored 72 h after CCl<jats:sub>4<\/jats:sub> exposure. We concluded that Egr-1 was required for prompt cell-cycle entry (G0- to G1-phase) and G1\/S-phase transition after toxic liver injury. These data support the hypothesis that Egr-1 provides hepatoprotection in the CCl<jats:sub>4<\/jats:sub>-injured liver, attributable, in part, to timely cell-cycle induction and progression. <\/jats:p>","DOI":"10.1152\/ajpgi.00544.2010","type":"journal-article","created":{"date-parts":[[2011,3,18]],"date-time":"2011-03-18T04:53:19Z","timestamp":1300423999000},"page":"G1124-G1131","source":"Crossref","is-referenced-by-count":29,"title":["Early growth response (EGR)-1 is required for timely cell-cycle entry and progression in hepatocytes after acute carbon tetrachloride exposure in mice"],"prefix":"10.1152","volume":"300","author":[{"given":"Michele T.","family":"Pritchard","sequence":"first","affiliation":[{"name":"Departments of 1Pathobiology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert N.","family":"Malinak","sequence":"additional","affiliation":[{"name":"Departments of 1Pathobiology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura E.","family":"Nagy","sequence":"additional","affiliation":[{"name":"Departments of 1Pathobiology and"},{"name":"Gastroenterology, Cleveland Clinic,"},{"name":"Department of Molecular Medicine, Case Western Reserve University, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00399.2006"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.02.092"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(02)01055-7"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20969"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6603(08)60815-6"},{"key":"B6","first-page":"1173","volume":"12","author":"Geng Y","year":"1996","journal-title":"Oncogene"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103862200"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50145"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(03)00270-1"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5279.1219"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.17.9971"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M407969200"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1096\/fj.00-0909fje"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.02.065"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1080\/01926230590881808"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2003.12.005"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s12038-009-0034-2"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.04.017"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1097\/01.alc.0000189286.81943.51"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00325.2007"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.23.13829"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.21609"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1489"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-1007104"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00107.2009"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1006\/taap.2000.8952"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-1830"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.28.17795"}],"container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpgi.00544.2010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T03:00:57Z","timestamp":1567998057000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpgi.00544.2010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,6]]},"references-count":28,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2011,6]]}},"alternative-id":["10.1152\/ajpgi.00544.2010"],"URL":"https:\/\/doi.org\/10.1152\/ajpgi.00544.2010","relation":{},"ISSN":["0193-1857","1522-1547"],"issn-type":[{"value":"0193-1857","type":"print"},{"value":"1522-1547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,6]]}}}